Studies are designed to gain a more complete understanding of the sequence of molecular events involved in the action of insulin on fat cells. Insulin has been shown to initiate its actions on target tissues by interacting with specific receptors on the surface of the cell membrane. The metabolic events occurring immediately subsequent to this interaction are largely unknown. Fruitful information should be obtained concerning this phase of insulin action by investigating the mechanism of certain polyamines (spermidine and spermine) which are capable of influencing fat cell glucose and lipid metabolism in a manner similar to insulin. Polyamines are well suited for these studies since they mimic the action of insulin on the plasma membrane at a point subsequent to the insulin-receptor interaction. A second aim is to explain the differences in sensitivity of large and small fat cells (rat and human) to insulin and certain lipolytic hormones such as glucagon, ACTH and epinephrine. Large adipocytes in contrast to small adipocytes are less sensitive to the actions of insulin on glucose oxidation and lipolysis induced by theophylline. Similarly these cells are insensitive to the actions of lipolytic hormones. Investigations of hormone binding, glucose and 3-O-methyl transport, phosphodiesterase and adenyl cyclase will be carried out in an attempt to localize, at the cellular level, the alterations responsible for hormone insensitivity.